.svg)
Lindsay J. Talbot, MD | St. Jude Children's Research Hospital
Modulating myeloid immunosuppression to improve CAR T-cell therapy using a novel patient-derived humanized mouse platform
Granted by All 2026 Family Funds
This research project aims to improve CAR T-cell therapy for osteosarcoma. Dr. Talbot has developed a new laboratory model using bone marrow cells collected from osteosarcoma patients during surgery, which can be used to recreate key parts of the patient's immune system in mice. This model helps study how certain immune cells, called myeloid cells, can suppress CAR T-cell activity and limit the effectiveness of immunotherapy. Dr. Talbot will test whether combining CAR T-cells with drugs that target these suppressive myeloid cells can improve cancer control. The ultimate goal is to create a more accurate way to evaluate and accelerate promising immunotherapies for osteosarcoma and other solid tumors.
Dr. Lindsay Talbot is a surgeon-scientist at St. Jude Children’s Research Hospital. She performs the full spectrum of pediatric oncology surgery and is a core member of the Extremity Sarcoma and Limb Salvage team, evaluating all bone and soft-tissue sarcoma patients requiring surgery at the institution. Dr. Talbot is the institutional expert on metastasectomy care for osteosarcoma patients and serves as the site PI for COG study AOST2031. She is also a Co-PI for the institutional clinical trial 3CAR4OS, evaluating CAR T-cell therapy efficacy when given at the end of upfront chemotherapy for patients newly diagnosed with metastatic osteosarcoma. Her clinical and research programs are tightly integrated. She directs a basic science laboratory focused on preclinical development of next-generation CAR T-cell products. Her research seeks to improve CAR T-cell therapy for pediatric solid tumors, particularly osteosarcoma, through enhanced chemokine-mediated homing of CAR T-cells, studies of mediators of CAR T-cell failure, and improved orthotopic, immunocompetent, and humanized modeling of pediatric solid tumors for high-fidelity translational applications.
Seth M. Pollack, MD | Northwestern University
A Novel Strategy for Altering Osteosarcoma Macrophages to Allow Immunotherapy
This research project is exploring a new way to help the immune system recognize and fight osteosarcoma by studying how blocking a signaling pathway called CXCL12/CXCR4 can change the tumor environment, allowing cancer-fighting immune cells to enter tumors more effectively. Early results show that combining this approach with interferon, a natural immune-boosting protein, can reduce tumor growth and make immune cells more active against cancer. Dr. Pollack’s lab will test this strategy in advanced laboratory models to better understand how it works and identify the patients most likely to benefit.
Seth M. Pollack, MD, is a physician-scientist and Professor with tenure at Northwestern University Feinberg School of Medicine, where he serves as Director of the Sarcoma Program and Co-Leader of the Cancer Immunology and Immunotherapy Initiative and the Translational Research in Malignancies Program at the Robert H. Lurie Comprehensive Cancer Center. His research focuses on developing and translating immunotherapies for sarcoma with an emphasis on understanding and overcoming the immunosuppressive tumor microenvironment. Dr. Pollack has led investigator-initiated clinical trials in adoptive T cell therapy and cytokine-based immunotherapy, integrating correlative science to inform next-generation treatments. His work bridges basic tumor immunology and clinical translation, with the goal of improving outcomes for patients with rare and difficult-to-treat cancers.
Theodore S. Nowicki, MD, PhD | University of California, Los Angeles
TNF-alpha-armed CAR-T cell therapies for osteosarcoma
This research project is developing a new type of CAR T-cell therapy for osteosarcoma, engineered CAR T-cells to target a protein called GD2 on tumor cells while also releasing TNF-alpha, a natural immune molecule that helps the cells attack cancer and overcome the tumor’s defenses. The Nowicki lab will test whether these enhanced CAR T-cells can kill tumors more effectively and safely than current CAR T-cell approaches. They will also study how the therapy changes the tumor environment to better support an immune response against cancer.
Dr. Nowicki is a cellular immunologist, pediatric oncologist, and laboratory principal investigator. His area of interest is in T-cell-based cancer immunotherapy, determining biological differences between responders and non-responders to these therapies, and using this information to further improve these cellular immunotherapeutics. This research approach includes characterizing the evolution of transgenic cellular immunotherapeutics over time in patients at the epigenomic, phenotypic, and functional levels, and correlating these phenomena with clinical response or non-response, as well as the development of toxicities. His lab then utilizes this information to reverse engineer novel therapeutic strategies to overcome existing limitations on T-cell-based immunotherapies and improve both clinical responses and toxicity profiles. Dr. Nowicki has published multiple studies in this area, including for cell therapies for leukemias/lymphomas, and more broadly in cell therapies for solid tumors.
Alice Browne, PhD | National Cancer Institute
A novel extracellular matrix remodeling therapeutic strategy in osteosarcoma
This project focuses on the extracellular matrix and its impact on osteosarcoma progression and metastasis. Dr. Browne is developing a novel cell therapy approach to modulate hyaluronic acid, a key ECM component elevated in osteosarcoma. This work provides a new opportunity to develop a clinical biomarker and therapeutic strategy for the clinic, in combination with standard chemotherapy and T cell therapies. These studies will support an IND for a clinical trial providing treatment options for patients.
Alice Browne, PhD, is a postdoctoral fellow in the Pediatric Oncology Branch at the National Cancer Institute, working in the laboratory of Dr. Rosandra Kaplan. Her research focuses on developing novel cellular therapies that target the tumor microenvironment in pediatric cancers, with an emphasis on extracellular matrix remodeling and the role of hyaluronic acid in driving immune exclusion and therapeutic resistance. She leads the development of genetically engineered mesenchymal stromal cell (MSC) therapies designed to enhance drug delivery and improve responses to chemotherapy and immunotherapy. Alice completed her PhD in Medicine at Queen’s University Belfast in collaboration with the NIH. Her work integrates translational cancer biology, advanced imaging, and cell therapy approaches to develop clinically actionable strategies for high-risk solid tumors.
Andrew Wahba, MD | Baylor College of Medicine/Texas Children’s Hospital
Advancing Pediatric Cancer Immunotherapy with CAR-NKT Cells
This research project is developing a new type of immunotherapy for osteosarcoma that uses specialized immune cells called invariant natural killer T (iNKT) cells to find and destroy cancer. Dr. Wahba is engineering these cells to recognize a protein commonly found on osteosarcoma tumors, enhance their cancer-fighting activity, and include a built-in safety switch to improve patient safety. Because iNKT cells naturally travel into tumors more effectively than many other immune cells, they may be better able to overcome the challenges that have limited other immunotherapies for solid tumors. The team will test this approach in laboratory and animal models to evaluate its effectiveness and understand how the cells reach and function within tumors. This study will generate IND-enabling data to advance this dual-targeted, cytokine-enhanced CAR-NKT therapy toward a first-in-human clinical trial for children with relapsed or refractory osteosarcoma.
Dr. Andrew Wahba is a faculty member in the Division of Pediatric Hematology–Oncology at Baylor College of Medicine and Texas Children’s Hospital and a physician-scientist in the Center for Advanced Innate Cell Therapy (AICT). He provides comprehensive clinical care for children with solid tumors and serves as a co-investigator on multiple ongoing Phase I studies, including cell-based immunotherapy trials. His research focuses on developing novel immunotherapies for children with relapsed or refractory cancers, with a particular emphasis on chimeric antigen receptor (CAR)-engineered natural killer T (NKT) cells, with the goal of translating laboratory discoveries into first-in-human clinical trials. He received his medical degree from Cairo University and completed his residency and research training at UT MD Anderson Cancer Center and is committed to advancing translational research to improve outcomes for children with osteosarcoma.
